1. Field of the Invention
Trichothecenes are a closely related group of biologically active secondary metabolites produced by certain species of Fusarium and by related fungal genera in the class Hyphomycetes. Production of the toxins in agricultural commodities has led to a variety of mycotoxicoses in man and animal. The Fusaria occur widely in nature on many hosts and substrates and are among the most common of all the fungi.
It is well established that the trichothecene skeleton is formed by mevalonate via farnesyl pyrophosphate and trichodiene [Ciegler, J. Food Protec. 42: 825-828 (1979)]. All toxic trichothecenes possess a 12,13-epoxy-.DELTA..sup. 9 nucleus, which is believed to be formed via oxygenation of trichodiene. Desjardins et al. [Appl. Environ. Microbiol. 51: 493-497 (1986)] have shown that the oxygens of the pyran nucleus, the 12,13-epoxide, and the various hydroxyl groups are all derived from molecular oxygen. It may be concluded that these six oxygenations are catalyzed by aliphatic hydroxylases which are either dioxygenases or monooxygenases. These enzyme mechanisms can be distinguished by their sensitivity to a variety of inhibitors. In the course of studying the effects of several known and presumptive monooxygenase inhibitors and analogous compounds on trichothecene biosynthesis in Fusarium sporotrichioides, which produces T-2 toxin as the end product, and Fusarium sambucinum, which produces diacetoxyscirpenol as the end product, I have arrived at the subject invention.
2. Description of the Prior Art
One such inhibitor I have investigated is ancymidol. Ancymidol has been reported in the literature as having plant growth regulator activity at concentrations less than 10.sup.-6 M (0.2 .mu.g./ml.). Inhibition of plant growth by ancymidol was first demonstrated by Tschabold et al. [Plant Physiol. 46: 19 (1970)]. Leopold [Plant Physiol. 48: 537-540 (1971)] and Shive and Sisler [Plant Physiol. 57: 640-644 (1976)] determined that gibberellin relieved the growth retardation by ancymidol in lettuce hypocotyls, green bean plants, and corn seedlings. Coolbaugh et al. [Plant Physiol. 57: 245-248 (1976) and Plant Physiol. 69: 707-711 (1982)] found that ancymidol blocked three oxidative reactions in the gibberellin biosynthetic pathway in higher plants.
Ancymidol is also weakly fungitoxic. Shive and Sisler, supra, found ancymidol at 100 .mu.g./ml. to inhibit dry weight increase of Gibberella fujikuroi by 23%. However, no concentration was found where dry weight was not affected and gibberellin activity produced was affected. Ali [Can. J. Bot. 57: 458-460 (1979)] showed ancymidol at 4 .mu.g./ml. to inhibit radial growth of Fusarium graminearum by 50%. Coolbaugh et al. [Plant Physiol. 69: 712-716 (1982)] found ancymidol at 10.sup.-3 M (250 .mu.g./ml.) to inhibit dry weight increase of Gibberella fujikuroi by 88%. They also showed that ancymidol was much less effective in inhibiting gibberellin biosynthesis in the fungus than in higher plants. Effects of ancymidol on other fungal enzyme systems were not studied.